Dental pulp stem cells (DPSCs) are stem cells present in the dental pulp, which is the soft living tissue within teeth. DPSCs can be collected from dental pulp by means of a non-invasive practice. It can be performed with an adult after simple extraction or to the young after surgical extraction of wisdom teeth. [1] They are pluripotent, as they can form embryoid body-like structures (EBs) in vitro and teratoma-like structures that contained tissues derived from all three embryonic germ layers when injected in nude mice. [2] DPSCs can differentiate in vitro into tissues that have similar characteristics to mesoderm, endoderm and ectoderm layers. [2] They can differentiate into many cell types, such as odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. DPSCs were found to be able to differentiate into adipocytes and neural-like cells. [3] DPSC differentiation into osteogenic lines is enhanced in 3D condition and hypoxia. [4] These cells can be obtained from postnatal teeth, wisdom teeth, and deciduous teeth, providing researchers with a non-invasive method of extracting stem cells. [5] The different cell populations, however, differ in certain aspects of their growth rate in culture, marker gene expression and cell differentiation, although the extent to which these differences can be attributed to tissue of origin, function or culture conditions remains unclear. [6] As a result, DPSCs have been thought of as an extremely promising source of cells used in endogenous tissue engineering. [7]
Studies have shown that the proliferation rate of DPSCs is 30% higher than in other stem cells, such as bone marrow stromal stem cells (BMSSCs). [8] These characteristics of DPSCs are mainly due to the fact that they exhibit elevated amounts of cell cycling molecules, one being cyclin-dependent kinase 6 (CDK6), present in the dental pulp tissue. [8] Additionally, DPSCs have displayed lower immunogenicity than MSCs. [9]
Atari et al., established a protocol for isolating and identifying the subpopulations of dental pulp pluripotent-like stem cells (DPPSC). These cells are SSEA4+, OCT3/4+, NANOG+, SOX2+, LIN28+, CD13+, CD105+, CD34-, CD45-, CD90+, CD29+, CD73+, STRO1+, and CD146-, and they show genetic stability in vitro based on genomic analysis with a newly described CGH technique. [2]
The human mouth is vulnerable to craniofacial defects, microbial attacks, and traumatic damages. [10] Although preclinical and clinical partial regeneration of dental tissues has shown success, the creation of an entire tooth from DPSCs is not yet possible. [10]
Distraction osteogenesis (DO) is a method of bone regeneration, commonly used in the surgical repair of large craniofacial defects. [7] The area in which the defect is present is purposely broken in surgery, allowed to heal briefly, and then the bone segments are gradually separated until the area has healed satisfactorily. A study conducted in 2018 by Song et al. found that DPSCs transfected with Sirtuin-1 (SIRT1) in rabbits were more effective in promoting bone formation during DO. [7] SIRT1 directly regulated MSCs into osteoblasts which then shows the accumulation of significantly higher levels of calcium after osteogenic differentiation in vitro, suggesting the potential role of DPSCs in enhancing the efficiency of DO. [7]
Calcine tooth powder (CTP) is obtained by burning extracted teeth, destroying the potential infection-causing material within the tooth, resulting in tooth ash [11] Tooth ash has been shown to promote bone repair. [12] Although recent studies have shown that calcine tooth powder- culture media (CTP-CM) does not affect proliferation, they have shown that CTP-CM has significantly increased levels of osteo/odontogenic markers in DPSCs. [11]
Stem cells from human exfoliated deciduous teeth (SHED) are similar to DPSCs in the sense that they are both derived from the dental pulp, but SHED are derived from baby teeth, whereas DPSCs are derived from adult teeth. SHED are a population of multipotent stem cells that are easily collected, as deciduous teeth either shed naturally or are physically removed in order to facilitate the proper growth of permanent teeth. [13] [14] These cells can differentiate into osteocytes, adipocytes, odontoblast, and chondrocytes in vitro. [14] Recent work has shown the enhanced proliferative capabilities of SHED when compared with that of dental pulp stem cells. [14]
Studies have shown that under the influence of oxidative stress, SHED (OST-SHED) displayed increased levels of neuronal protection. [15] The properties of these cells exhibited in this study suggest that OST-SHED could potentially prevent of oxidative stress-induced brain damage and could aid in the development of therapeutic tools for neurodegenerative disorders. [15] After SHED injection into Goto-Kakizaki rats, type II diabetes mellitus (T2DM) was ameliorated, suggesting the potential for SHED in T2DM therapies. [16]
Recent studies have also shown that the administration of SHED in mice ameliorated the T cell immune imbalance in allergic rhinitis (AR), suggesting the cells' potential in future AR treatments. [17] After introducing SHED, mice experienced reduced nasal symptoms and decreased inflammatory infiltration. [17] SHEDs were found to inhibit the proliferation of T lymphocytes, increase levels of an anti-inflammatory cytokine, IL-10, and decrease the levels of a pro-inflammatory cytokine, IL-4. [17]
Additionally, SHED can potentially treat liver cirrhosis. [18] In a study conducted by Yokoyama et al. (2019), SHED were differentiated into hepatic stellate cells. [18] They found that when hepatic cells derived from SHED were transplanted into the liver of rats, liver fibrosis was terminated, allowing for the healing of the liver structure. [18]
Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells. Isolating the inner cell mass (embryoblast) using immunosurgery results in destruction of the blastocyst, a process which raises ethical issues, including whether or not embryos at the pre-implantation stage have the same moral considerations as embryos in the post-implantation stage of development.
The pulp is the connective tissue, nerves, blood vessels, and odontoblasts that comprise the innermost layer of a tooth. The pulp's activity and signalling processes regulate its behaviour.
Ameloblasts are cells present only during tooth development that deposit tooth enamel, which is the hard outermost layer of the tooth forming the surface of the crown.
Deciduous teeth or primary teeth, also informally known as baby teeth, milk teeth, or temporary teeth, are the first set of teeth in the growth and development of humans and other diphyodonts, which include most mammals but not elephants, kangaroos, or manatees, which are polyphyodonts. Deciduous teeth develop during the embryonic stage of development and erupt during infancy. They are usually lost and replaced by permanent teeth, but in the absence of their permanent replacements, they can remain functional for many years into adulthood.
The periodontal ligament, commonly abbreviated as the PDL, is a group of specialized connective tissue fibers that essentially attach a tooth to the alveolar bone within which it sits. It inserts into root cementum on one side and onto alveolar bone on the other.
The enamel organ, also known as the dental organ, is a cellular aggregation seen in a developing tooth and it lies above the dental papilla. The enamel organ which is differentiated from the primitive oral epithelium lining the stomodeum. The enamel organ is responsible for the formation of enamel, initiation of dentine formation, establishment of the shape of a tooth's crown, and establishment of the dentoenamel junction.
In vertebrates, an odontoblast is a cell of neural crest origin that is part of the outer surface of the dental pulp, and whose biological function is dentinogenesis, which is the formation of dentin, the substance beneath the tooth enamel on the crown and the cementum on the root.
Regenerative medicine deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function". This field holds the promise of engineering damaged tissues and organs by stimulating the body's own repair mechanisms to functionally heal previously irreparable tissues or organs.
The dental follicle, also known as dental sac, is made up of mesenchymal cells and fibres surrounding the enamel organ and dental papilla of a developing tooth. It is a vascular fibrous sac containing the developing tooth and its odontogenic organ. The dental follicle (DF) differentiates into the periodontal ligament. In addition, it may be the precursor of other cells of the periodontium, including osteoblasts, cementoblasts and fibroblasts. They develop into the alveolar bone, the cementum with Sharpey's fibers and the periodontal ligament fibers respectively. Similar to dental papilla, the dental follicle provides nutrition to the enamel organ and dental papilla and also have an extremely rich blood supply.
Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. Also known as somatic stem cells, they can be found in juvenile, adult animals, and humans, unlike embryonic stem cells.
A stem cell line is a group of stem cells that is cultured in vitro and can be propagated indefinitely. Stem cell lines are derived from either animal or human tissues and come from one of three sources: embryonic stem cells, adult stem cells, or induced stem cells. They are commonly used in research and regenerative medicine.
Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition. As of 2016, the only established therapy using stem cells is hematopoietic stem cell transplantation. This usually takes the form of a bone-marrow transplantation, but the cells can also be derived from umbilical cord blood. Research is underway to develop various sources for stem cells as well as to apply stem-cell treatments for neurodegenerative diseases and conditions such as diabetes and heart disease.
Nestin is a protein that in humans is encoded by the NES gene.
Transcription factor Sp7, also called osterix (Osx), is a protein that in humans is encoded by the SP7 gene. It is a member of the Sp family of zinc-finger transcription factors It is highly conserved among bone-forming vertebrate species It plays a major role, along with Runx2 and Dlx5 in driving the differentiation of mesenchymal precursor cells into osteoblasts and eventually osteocytes. Sp7 also plays a regulatory role by inhibiting chondrocyte differentiation maintaining the balance between differentiation of mesenchymal precursor cells into ossified bone or cartilage. Mutations of this gene have been associated with multiple dysfunctional bone phenotypes in vertebrates. During development, a mouse embryo model with Sp7 expression knocked out had no formation of bone tissue. Through the use of GWAS studies, the Sp7 locus in humans has been strongly associated with bone mass density. In addition there is significant genetic evidence for its role in diseases such as Osteogenesis imperfecta (OI).
Resorption of the root of the tooth, or root resorption, is the progressive loss of dentin and cementum by the action of odontoclasts. Root resorption is a normal physiological process that occurs in the exfoliation of the primary dentition. However, pathological root resorption occurs in the permanent or secondary dentition and sometimes in the primary dentition.
Mesenchymal stem cells (MSCs) also known as mesenchymal stromal cells or medicinal signaling cells are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts, chondrocytes, myocytes and adipocytes.
Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor or unipotent – (iUSC) according to their developmental potential and degree of dedifferentiation. Progenitors are obtained by so-called direct reprogramming or directed differentiation and are also called induced somatic stem cells.
Regenerative endodontic procedures is defined as biologically based procedures designed to replace damaged structures such as dentin, root structures, and cells of the pulp-dentin complex. This new treatment modality aims to promote normal function of the pulp. It has become an alternative to heal apical periodontitis. Regenerative endodontics is the extension of root canal therapy. Conventional root canal therapy cleans and fills the pulp chamber with biologically inert material after destruction of the pulp due to dental caries, congenital deformity or trauma. Regenerative endodontics instead seeks to replace live tissue in the pulp chamber. The ultimate goal of regenerative endodontic procedures is to regenerate the tissues and the normal function of the dentin-pulp complex.
Craniofacial regeneration refers to the biological process by which the skull and face regrow to heal an injury. This page covers birth defects and injuries related to the craniofacial region, the mechanisms behind the regeneration, the medical application of these processes, and the scientific research conducted on this specific regeneration. This regeneration is not to be confused with tooth regeneration. Craniofacial regrowth is broadly related to the mechanisms of general bone healing.
Professor Alastair J Sloan is an applied bioscientist and expert in the broad field of mineralised connective tissues, and since January 2020 current head of the Melbourne Dental School, University of Melbourne.